Author Correction: Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

Emmanuelle Souzeau, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this Article. This has now been corrected in both the PDF and HTML versions of the Article

Validation of an intrinsic groundwater pollution vulnerability methodology using a national nitrate database.

The importance of groundwater for potable supply, and the many sources of anthropogenic contamination, has led to the development of intrinsic groundwater vulnerability mapping. An Analysis of Co-Variance and Analysis of Variance are used to validate the extensively applied UK methodology, based upon nitrate concentrations from 1,108 boreholes throughout England and Wales. These largely confirm the current aquifer and soil leaching potential classifications and demonstrate the benefits of combining soil and low permeability drift information. European legislation such as the Water Framework Directive will require more dynamic assessments of pollutant risk to groundwater. These results demonstrate that a number of improvements are required to future intrinsic groundwater vulnerability methodologies. The vertical succession of geological units must be included, so that non-aquifers can be zoned in the same way as aquifers for water supply purposes, while at the same time recognising their role in influencing the quality of groundwater in deeper aquifers. Classifications within intrinsic vulnerability methodologies should be based upon defined diagnostic properties rather than expert judgement. Finally the incorporation into groundwater vulnerability methodologies of preferential flow in relation to geological deposits, soil type and land management practices represents a significant, but important, future challenge

Genome-wide association study of primary open-angle glaucoma in continental and admixed African populations

Contains fulltext : 200131.pdf (publisher's version ) (Open Access)Primary open angle glaucoma (POAG) is a complex disease with a major genetic contribution. Its prevalence varies greatly among ethnic groups, and is up to five times more frequent in black African populations compared to Europeans. So far, worldwide efforts to elucidate the genetic complexity of POAG in African populations has been limited. We conducted a genome-wide association study in 1113 POAG cases and 1826 controls from Tanzanian, South African and African American study samples. Apart from confirming evidence of association at TXNRD2 (rs16984299; OR[T] 1.20; P = 0.003), we found that a genetic risk score combining the effects of the 15 previously reported POAG loci was significantly associated with POAG in our samples (OR 1.56; 95% CI 1.26-1.93; P = 4.79 x 10(-5)). By genome-wide association testing we identified a novel candidate locus, rs141186647, harboring EXOC4 (OR[A] 0.48; P = 3.75 x 10(-8)), a gene transcribing a component of the exocyst complex involved in vesicle transport. The low frequency and high degree of genetic heterogeneity at this region hampered validation of this finding in predominantly West-African replication sets. Our results suggest that established genetic risk factors play a role in African POAG, however, they do not explain the higher disease load. The high heterogeneity within Africans remains a challenge to identify the genetic commonalities for POAG in this ethnicity, and demands studies of extremely large size

Recent insights into endothelial control of leukocyte extravasation

In the process of leukocyte migration from the circulation across the vascular wall, the crosstalk with endothelial cells that line the blood vessels is essential. It is now firmly established that in endothelial cells important signaling events are initiated upon leukocyte adhesion that impinge on the regulation of cell-cell contact and control the efficiency of transendothelial migration. In addition, several external factors such as shear force and vascular stiffness were recently identified as important regulators of endothelial signaling and, consequently, leukocyte transmigration. Here, I review recent insights into endothelial signaling events that are linked to leukocyte migration across the vessel wall. In this field, protein phosphorylation and Rho-mediated cytoskeletal dynamics are still widely studied using increasingly sophisticated mouse models. In addition, activation of tyrosine phosphatases, changes in endothelial cell stiffness as well as different vascular beds have all been established as important factors in endothelial signaling and leukocyte transmigration. Finally, I address less-well-studied but interesting components in the endothelium that also control transendothelial migration, such as the ephrins and their Eph receptors, that provide novel insights in the complexity associated with this proces